Gene最新文献

{"title":"PRDM14 promotes the bovine somatic stem cell reprogramming through enhancing oxidative phosphorylation at the initial stage","authors":"Qingqing Wei ,&nbsp;Wenhui Li ,&nbsp;Guina Cui ,&nbsp;Yiliang Xu ,&nbsp;Shaorong Gao","doi":"10.1016/j.gene.2025.149978","DOIUrl":"10.1016/j.gene.2025.149978","url":null,"abstract":"<div><div>Bovine induced pluripotent stem cells (biPSCs), which can be obtained through somatic cells reprogramming have multiple potential applications in human disease, regeneration medicine and biotechnical animal breeding. However, the low reprogramming efficiency and poorly exploration of the mechanism underlying the somatic cells reprogramming in cattle restricted the applications of biPSCs. Here, we reported the transcription factor PR-domain containing protein 14 (<em>PRDM14</em>) was highly expressed in bovine fetal testis and intestine. And the expression of <em>PRDM14</em> showed the lowest level in bovine embryonic fibroblasts (BEF), increased on day 3 and day 18, and finally reached the highest level in induced pluripotent stem cells (iPSCs) during the reprogramming induced by <em>OCT4</em>, <em>SOX2</em>, <em>KLF4</em> and <em>MYC</em> (OSKM). In a gain-of-function assay, we showed that <em>PRDM14</em> was able to enhance the efficiency of reprogramming from BEF in conjunction with bovine OSKM. While, silencing of <em>PRDM14</em> inhibited the reprogramming efficiency of BEF. The bovine iPSCs derived from OSKM plus <em>PRDM14</em> displayed normal karyotype, expressed pluripotent markers and could differentiated into three germ layers in vitro. Transcriptome analysis of cells at the early, median and late reprogramming stages revealed that several genes involved in oxidative phosphorylation (OXPHOS) are upregulated on day 3 when OXPHOS burst occurs, while downregulated on day 15 when OXPHOS transmits to glycolysis, by ectopic expression of <em>PRDM14</em>. RT-qPCR and ATP content detection further confirmed that <em>PRDM14</em> could improve somatic cells reprogramming by enhancing OXPHOS at the early stage. Additionally, forced expression of <em>PRDM14</em> in OSKM-induced biPSCs showed that it upregulates the expression of key pluripotency gene <em>NANOG</em> but downregulates <em>LIN28</em>, DNA methylation genes <em>DNMT1</em>/<em>3B</em> and DNA demethylation genes <em>TET1</em>/<em>2</em>/<em>3</em>. Altogether, our study uncovers <em>PRDM14</em> exemplifies a key transcription factor required for the reacquisition of pluripotency in bovine somatic cells and the maintenance of bovine iPSCs identity.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149978"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro expression and seroreactivity of Toxoplasma gondii GRA1 protein encoded by unmodified and nucleoside-modified mRNA constructs","authors":"Mehmet Nadir Şahinci ,&nbsp;Mert Döşkaya ,&nbsp;Muhammet Karakavuk ,&nbsp;Seren Kaplan ,&nbsp;Gizem Mutlu ,&nbsp;Tuğçe Gizem Perçin ,&nbsp;Sedef Erkunt Alak ,&nbsp;Özlem Günay-Esiyok ,&nbsp;Aytül Gül Mete ,&nbsp;Aysu Değirmenci Döşkaya ,&nbsp;Ayşe Gülten Kantarcı ,&nbsp;Adnan Yüksel Gürüz ,&nbsp;Hüseyin Can","doi":"10.1016/j.gene.2025.149965","DOIUrl":"10.1016/j.gene.2025.149965","url":null,"abstract":"<div><div>Toxoplasmosis is an infectious parasitic disease caused by <em>Toxoplasma gondii</em>, with a global seroprevalence estimated to affect more than one-third of the human population. <em>T. gondii</em> can be a serious health concern for pregnant women and immunocompromised patients. Currently, there is no effective and safe vaccine for humans. However, mRNA technology is a promising platform to develop efficient and safe vaccines against toxoplasmosis. Therefore, we designed nucleoside-modified and unmodified mRNA vaccine transcripts expressing <em>T. gondii</em> recombinant GRA1 protein and analyzed their <em>in vitro</em> protein expression profile as well as potential immunogenicity using IFAT, Western blot, and ELISA. Moreover, to compare translational efficiency, poly-A tail was extended with an extra ∼150 bp in addition to the existing ∼120 bp poly-A tail in two distinct mRNA designs. The results showed that all four mRNA constructs expressed rGRA1 protein in HEK293T cells. However, mRNA constructs with extended poly-A tails exhibited reduced expression level of rGRA1 protein compared to other mRNA vaccine transcripts. Additionally, unmodified mRNA construct with or without extended poly-A tail yielded significantly higher protein expression compared to nucleoside-modified mRNA constructs through ELISA using anti-polyhis antibody (P&lt;0.05). Western blot showed that rGRA1 protein expressed by all four mRNA constructs reacted strongly with <em>T. gondii</em> IgG seropositive mice sera. Furthermore, ELISA revealed that rGRA1 proteins derived from unmodified and nucleoside-modified mRNA constructs formed significantly stronger immune complexes with <em>T. gondii</em> IgG antibodies compared to negative controls (P&lt;0.05). These data suggest that both unmodified and nucleosidemodified mRNA constructs expressing rGRA1 protein have potential as vaccine candidates and warrant further investigation for development of an mRNA-based vaccine against toxoplasmosis. However, encapsulation of the produced mRNA constructs in LNPs and <em>in vivo</em> studies are required to validate these preliminary results.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149965"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 delays chronological aging in a yeast model via SSE1-Mediated mitophagy","authors":"Ze Yao ,&nbsp;Ming Lu ,&nbsp;Chunshuang Li ,&nbsp;Xiang Li ,&nbsp;Hui Shang ,&nbsp;Songtao Bie","doi":"10.1016/j.gene.2025.149986","DOIUrl":"10.1016/j.gene.2025.149986","url":null,"abstract":"<div><div>Ginsenoside Rg1 (Rg1), an active compound in <em>Panax ginseng</em> C. A. Meyer (ginseng), has shown potential to ameliorate age-related cell damage and extend lifespan in multiple model organisms. However, the precise molecular mechanisms of its anti-aging effects remain unclear. In this study, we explore the anti-aging mechanisms of ginsenoside Rg1, focusing on its impact on mitophagy in <em>Saccharomyces cerevisiae</em>. Using propidium iodide staining, we found that Rg1 extends the chronological lifespan (CLS) of yeast cells. Further analyses revealed that Rg1 enhances mitochondrial function and antioxidant capacity in yeast cells by inducing mitophagy. Moreover, RNA-Seq and bioinformatics analyses identified the molecular chaperone <em>SSE1</em> as a key target of Rg1. <em>SSE1</em> knockout strain demonstrated that Rg1 enhances mitochondrial function and antioxidant capacity through <em>SSE1</em>-dependent mitophagy, thereby extending cell lifespan. Collectively, we concluded that Rg1 exerts its anti-aging effects through <em>SSE1</em>-mediated mitophagy. This study advances our understanding of Rg1-mediated mitophagy and mitochondrial regulation via <em>SSE1</em>, offering a foundation for the rational design of targeted anti-aging treatments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149986"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC","authors":"Hongxia Deng ,&nbsp;Dong Ye ,&nbsp;Shijie Qiu ,&nbsp;Shuang Ye ,&nbsp;Chongchang Zhou ,&nbsp;Shuai Fang ,&nbsp;Yuna Zhang ,&nbsp;Shanshan Gu","doi":"10.1016/j.gene.2025.149967","DOIUrl":"10.1016/j.gene.2025.149967","url":null,"abstract":"<div><h3>Objective</h3><div>Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.</div></div><div><h3>Methods</h3><div>Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).</div></div><div><h3>Results</h3><div>tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.</div></div><div><h3>Conclusions</h3><div>The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149967"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel candidate missense variant in the catalytic domain of USP26 associated with asthenoteratozoospermia","authors":"Seyedeh Zahra Mousavi ,&nbsp;Masomeh Askari ,&nbsp;Ken McElreavey ,&nbsp;Anu Bashamboo ,&nbsp;Najmeh Salehi ,&nbsp;Mandana Rastari ,&nbsp;Zeynab Rokhsattalab ,&nbsp;Bahram Mohammad Soltani ,&nbsp;Mehdi Totonchi","doi":"10.1016/j.gene.2025.149945","DOIUrl":"10.1016/j.gene.2025.149945","url":null,"abstract":"<div><h3>Introduction</h3><div>Teratozoospermia, characterized by abnormal sperm morphology, is a significant factor contributing to the male infertility. Deubiquitinating enzymes play a crucial role in controlling protein synthesis and degradation during spermatogenesis.</div></div><div><h3>Methods</h3><div>Whole exome sequencing (WES) and the following insilico analysis were performed to detect the associated variant with asthenoteratozoospermia in a consanguineous Iranian family with two affected brothers.</div></div><div><h3>Results</h3><div>WES identified a novel candidate hemizygous missense mutation (chrX-132161044 T &gt; G:NM_031907.2:c.1205A &gt; C, p.Asn402Thr) in the catalytic domain of the <em>USP26</em> (Ubiquitin-Specific Peptidase 26) deubiquitinating enzyme in two affected siblings. The <em>USP26</em> encodes a testis-specific deubiquitinating enzyme which is necessary for normal spermatogenesis and may influence male fertility. The mutation changes asparagine 402 (N) into threonine (T) and was co-segregated with phenotype in other available family members. In-silico predictions indicate that the N402T change not only leads to the absence of <em>a</em> hydrogen bond between the mutant N402T and F430 residues but also causes a reduction in <em>USP26</em> protein stability, potentially resulting in defects in <em>USP26</em> enzymatic activity.</div></div><div><h3>Conclusions</h3><div>Our findings support a potential role for <em>USP26</em> variants contributing to asthenoteratozoospermia.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149945"},"PeriodicalIF":2.4,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: a meta-analysis” [Gene 525 (2013) 35–40]","authors":"Wei Cui,&nbsp;Cui-Ming Sun,&nbsp;Bao-Cheng Deng,&nbsp;Pei Liu","doi":"10.1016/j.gene.2025.149947","DOIUrl":"10.1016/j.gene.2025.149947","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149947"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants” [Gene 505 (2012) 66-74]","authors":"Jian Min Zhang ,&nbsp;Xi Jun Cui ,&nbsp;Yun Qiang Xia ,&nbsp;Sen Guo","doi":"10.1016/j.gene.2025.149948","DOIUrl":"10.1016/j.gene.2025.149948","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149948"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Under the dual hit: genetic and phenotypic analysis of a Han family with severe adolescent cirrhosis from the convergence of Wilson’s disease and favism","authors":"Yu-qin Xie ,&nbsp;Zi-yan Xu ,&nbsp;Hong Lin ,&nbsp;Li-jun Xie ,&nbsp;Jie-wei Luo ,&nbsp;Li-jun Zhang ,&nbsp;Zhi-hai Zheng","doi":"10.1016/j.gene.2025.149953","DOIUrl":"10.1016/j.gene.2025.149953","url":null,"abstract":"<div><div>Hepatolenticular degeneration (HLD, MIM:277900) is an autosomal recessive disorder characterized by excessive copper accumulation in hepatocytes, leading to hepatic and neurological abnormalities, hepatocellular injury, neurodegeneration, and copper deposition in the cornea. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic cause of hemolytic anemia, which can be triggered by chronic conditions, drugs, food, or infections, and exhibits highly variable severity. In some cases, multiple genetic factors may collectively influence disease presentation and progression. This study reports a proband who developed abnormal liver function at age 20. Four years later, she exhibited severe jaundice, liver dysfunction, serous effusions, anemia, and Kayser–Fleischer rings, leading to diagnoses including decompensated cirrhosis, splenomegaly, suspected HLD, hemolytic anemia, portal hypertension, hypoproteinemia, low T3 syndrome, primary peritonitis, and gallstones with cholecystitis. Genetic screening identified two pathogenic heterozygous variants in ATP7B (NM_000053.4): c.2128G &gt; A (p.G710S) in exon 8 and c.525dupA (p.V176Sfs*28) in exon 2, together forming a compound heterozygous mutation. Additionally, a heterozygous mutation in G6PD (NM_001360016.2), c.1388G &gt; A (p.R463H) in exon 12, was found. Family members carrying the G6PD variant showed recurrent benign jaundice or remained asymptomatic. A heterozygous missense variant of uncertain significance, c.205C &gt; T (p.R69C), was also detected in exon 3 of STEAP3 (NM_182915.3), a gene linked to hypochromic microcytic anemia with iron overload type 2 (MIM#615234). This rare variant was predicted to be deleterious by in silico tools, suggesting possible genetic cosegregation.</div><div>SWISS-MODEL analysis indicated that these variants may alter the three-dimensional structures of the copper-transporting ATPase and G6PD proteins, potentially impairing function—particularly the frameshift mutation p.V176Sfs*28. We hypothesize that the accumulation of multiple pathogenic genetic factors resulted in a “double-hit” effect, leading to the patient’s severe phenotypes, including advanced liver cirrhosis and hemolytic anemia. Elucidating such multi-gene “double-hit” mechanisms may enhance the understanding of gene–gene interactions in complex diseases.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149953"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trolline attenuates diabetic vascular injury by regulating SLC7A11-mediated ferroptosis and mitochondrial dysfunction","authors":"Wenbo Liu ,&nbsp;Cuifang Lu ,&nbsp;Bin Yang ,&nbsp;Ying Liu ,&nbsp;Jie Yan ,&nbsp;Tingyu Song ,&nbsp;Xiaofei Wang","doi":"10.1016/j.gene.2025.149968","DOIUrl":"10.1016/j.gene.2025.149968","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigated the therapeutic potential of Trolline, a natural compound, for alleviating high-glucose (HG)-induced vascular endothelial ferroptosis and mitochondrial dysfunction via the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) pathway.</div></div><div><h3>Materials and methods</h3><div>In db/db mice, inflammatory damage; glucose tolerance; and the expression of SLC7A11, glutathione peroxidase 4 (GPX4), and long-chain acyl-CoA synthetase family member 4 (ACSL4) were detected after treatment with Trolline. An HG-induced human microvascular endothelial cell (HMEC-1) injury model was established in vitro. Fe²⁺ deposition and GSH levels serve as important indicators of ferroptosis. The mitochondrial membrane potential and the cytoskeleton were determined by JC-1 and F-actin staining, respectively. The levels of apoptosis, cell cycle and reactive oxygen species (ROS) were determined by flow cytometry. Oxidative stress levels were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Ferroptosis- and inflammation-related protein expression in HMEC-1 cells was verified by Western blotting.</div></div><div><h3>Results</h3><div>In vivo experiments revealed that Trolline can lower blood sugar levels, alleviate inflammatory damage, and regulate the expression of ferroptosis-related proteins in db/db mice. In vitro experiments demonstrated that Trolline can alleviate various effects induced by HG. Under HG conditions, Trolline can inhibit apoptosis, reverse the cell cycle arrest in the SubG1 phase, reduce oxidative stress levels and Fe²⁺ overload, restore mitochondrial function, promote cytoskeletal remodelling, and regulate the expression of ferroptosis-related proteins. Mechanistically, ferroptosis inhibitors (Ferrostatin-1) and Trolline have the same protective effect on HMEC-1 cells in an HG environment. However, overexpression of SLC7A11 led to loss of the inhibitory effect of Trolline on ferroptosis, which confirms that the effect of Trolline is dependent on the SLC7A11-ferroptosis axis.</div></div><div><h3>Conclusion</h3><div>Trolline can alleviate diabetic vascular damage through SLC7A11-mediated inhibition of ferroptosis, improved mitochondrial function, and reduced oxidative inflammatory damage, providing a basis for the treatment of diabetic vascular complications.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149968"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expanding role of Furin in human Disease: A comprehensive review","authors":"Xinyang Li ,&nbsp;Chong Liu ,&nbsp;Haidi Hu","doi":"10.1016/j.gene.2025.149969","DOIUrl":"10.1016/j.gene.2025.149969","url":null,"abstract":"<div><div>Furin is a calcium-dependent serine endoprotease that activates multiple substrates by cleaving at polybasic motifs, playing a pivotal role in human physiology and pathology. This review summarizes the latest research progress regarding Furin’s extensive involvement in infectious diseases, tumor diseases, cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. This review offers an in-depth analysis of Furin’s dual functions, which include promoting viral entry into host cells, driving oncogenesis via growth factors, metalloproteinases, and the Notch signaling pathway, and maintaining metabolic homeostasis and immune tolerance. Key pathophysiological mechanisms involve the dysfunction of Furin substrate activation in atherosclerosis, hypertension, Alzheimer’s disease, diabetes, and other disorders. The review also highlights the potential value of Furin as a diagnostic and prognostic biomarker and therapeutic target, while pointing out the challenges encountered in developing its inhibitors.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149969"},"PeriodicalIF":2.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}